本研究发现,MMP-2,9在正常晶状体上皮细胞中未见表达,而在糖性白内障晶状体上皮中均有表达,且染色强,二者之间的表达差异有显著性。这表明在糖性白内障发病过程中,LEC过度表达Ⅳ型胶原酶,从而异常降解ECM,改变了LEC赖以正常生存、增殖的微环境,引起细胞转分化和基因表达异常。ECM的异常降解与糖性白内障晶状体前后囊下的纤维化有关。 调节MMP表达的因素有很多,其中TGF-β 1 的调节作用。近年来倍受关注。TGF-β 1 是一类具有多种功能的细胞因子,它对调控细胞的生长、分化及ECM的合成具有重要作用,与白内障的发生、发展密切相关;高血糖等损害因子活化激活的TGF-β 1[23] ,进而诱导MMP-2,9表达增强,使得ECM异常降解,LEC分化、增殖异常;异常分化、增殖的上皮细胞分泌TGF-β 1 增加,反馈性刺激MMP-2,9表达增强。此外,氧化应激的增强也能促使MMP表达增强 [4] 。 本研究发现,在正常的LEC中仅有少量的TGF-β 1 分布,且染色较淡,而糖性白内障的LEC中均有TGF-β 1 阳性表达,两者的阳性表达率差异有显著性,这提示TGF-β 1 在糖性白内障的发生过程中起着某种作用,而MMP-2,9与TGF-β 1 阳性表达呈正相关与Richiert等报道的结果一致 [5] ,他们采用酶谱法检测培养的小鸡的LEC MMP-2,9的分泌,发现TGF-β 1 呈时间和剂量依赖性诱导MMP-2,9的表达。TGF-β 1 可能通过调控MMP-2,9对糖性白内障的发生、发展起作用。TGF-β 1 、MMP-2,9在糖性白内障发生、发展中的确切作用及相互关系还需进一步研究。
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Expression and Significance of Transforming Growth Factor-β1 and Matrix Metalloproteinase-2,9in Human Diabetic Lens Epithelium XU Guo-xing,HU Jian-zhang,PAN Yong-ming,WANG Ting-ting,ZHENG Wei-dong,LIN Wen Fujian Institute of Ophthalmology,The First Affiliated Hospital,Fujian Medical University,Fuzhou350005,China ABSTRACT: Objective To investigate the expression and significance of transforming growth factor-β 1 (TGF-β 1 ),matrix metalloproteinase-2,9(MMP-2,9)in human diabetic lens epithelial cells(LEC). Methods Immunohistochemical staining was used to detect the expression of TGF-β 1 ,MMP-2,9in the diabetic LEC(23cases)and the normal LEC(7cases). Results There was significant difference of expression of TGF-β 1 and MMP-2,9between diabetic LEC and normal LEC(P<0.01). There was correlation between the expres-sion of TGF-β 1 and MMP-2,TGF-β 1 and MMP-9. Conclusion The expression of MMP-2,9indued by TGF-β 1 may play a critical role in the pathological fibrosis of anterior and posterior subcapsula during the development of diabetic cataract. KEY WORDS: cataract;transforming growth factor beta;metalloproteases
作者单位: 福建医科大学附属第一医院,福建省眼科研究所,福州 350005 作者简介: 徐国兴(1956~),男,教授. 上一页 [1] [2] |